Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated and what biological functions it plays. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using beam break counts from Drosophila activity monitors (DAMs). The number of laboratories worldwide studying sleep in Drosophila has grown from only a few 20 years ago to hundreds today. The utility of these studies is limited by the quality of the metrics that can be extracted from the data. Many software options exist to help analyze DAM data; however, these are often expensive or have significant limitations. Therefore, we describe here a method for analyzing DAM-based data using the sleep and circadian analysis MATLAB program (SCAMP). This user-friendly software has an advantage of combining several analyses of both sleep and circadian rhythms in one package and produces graphical outputs as well as spreadsheets of the outputs for further statistical analysis. The version of SCAMP described here is also the first published software package that can analyze data from multibeam DAM5Ms, enabling determination of positional preference over time.

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated by circadian rhythms, homeostatic sleep drive that builds up with wakefulness, and modifying factors such as hunger or social interactions, as well as about the biological functions of sleep. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using Drosophila activity monitors (DAMs). Here, we describe approaches for the activation of specific neurons of interest using optogenetics (involving genetic modifications that allow for light-based neuronal activation) and thermogenetics (involving genetic modifications that allow for temperature-based neuronal activation) so that researchers can evaluate the roles of those neurons in controlling rest and activity behavior. In this protocol, we describe how to set up a rig for simultaneous optogenetic or thermogenetic stimulation and activity monitoring for analysis of sleep and circadian rhythms in Drosophila, how to raise appropriate flies, and how to perform the experiment. This protocol will allow researchers to assess the causative role in the regulation of sleep and activity rhythms of any genetically tractable subset of cells.

BackgroundCOVID-19 pandemic restrictions may have influenced behaviours related to weight.AimTo describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic.Design and settingAn observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP.MethodClinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m2/year) were investigated using multivariable logistic regression.ResultsData were extracted on adults with T2D (n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension (n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = −0.1 kg/m2/year [interquartile range {IQR} −0.7–0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60–69 years versus 18–29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m2/year [IQR −0.6–0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D.ConclusionAmong adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions.

BackgroundOrlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM).AimTo explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes.Design and settingCohort study using anonymised health records from a UK database of general practice.MethodThe UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat’s associations with weight loss in those who had not been prescribed second-line antidiabetic medications.ResultsOut of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09).ConclusionOrlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss.

BackgroundMost people with type 2 diabetes receive treatment in primary care by GPs who are not specialised in diabetes. Thus, it is important to uncover the most essential information needs regarding type 2 diabetes in general practice.AimTo identify information needs related to type 2 diabetes for GPs.Design and settingSystematic review focused on literature relating to Western countries.MethodMEDLINE, Embase, PsycInfo and CINAHL were searched from inception to January 2024. Two researchers conducted the selection process, and citation searches were performed to identify any relevant articles missed by the database search. Quality appraisal was conducted with the Mixed Methods Appraisal Tool. Meaning units were coded individually, grouped into categories, and then studies were summarised within the context of these categories using narrative synthesis. An evidence map was created to highlight research gaps.ResultsThirty-nine included studies revealed eight main categories and 36 subcategories of information needs. Categories were organised into a comprehensive hierarchical model of information needs, suggesting ‘Knowledge of guidelines’ and ‘Reasons for referral’ as general information needs alongside more specific needs on ‘Medication’, ‘Management’, ‘Complications’, ‘Diagnosis’, ‘Risk factors’, and ‘Screening for diabetes’. The evidence map provides readers with the opportunity to explore the characteristics of the included studies in detail.ConclusionThis systematic review provides GPs, policymakers, and researchers with a hierarchical model of information and educational needs for GPs, and an evidence map showing gaps in the current literature. Information needs about clinical guidelines and reasons for referral to specialised care overlapped with needs for more specific information.

BackgroundIncident benzodiazepine prescriptions in primary care for anxiety decreased between 2003 and 2018. However, from 2008, incident prescribing of benzodiazepines for anxiety increased among those aged 18–34 years. There are increasing concerns around prescribing of benzodiazepines. Further, although guidelines state benzodiazepines should only be prescribed short term, in 2017, 44% of incident prescriptions were prescribed for longer than the recommended duration of 2–4 weeks.AimTo understand when and why GPs prescribe benzodiazepines for anxiety in young adults.Design and settingA qualitative study was undertaken using in-depth interviews with 17 GPs from 10 general practices in South West England.MethodInterviews were conducted by telephone or videocall. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and data analysed using reflexive thematic analysis.ResultsGPs described caution in prescribing benzodiazepines for anxiety in young adults, but thought they had an important role in acute situations. GPs described caution in prescribing duration, but some thought longer-term prescriptions could be appropriate. In light of these views, some GPs questioned whether primary care needs to revisit how clinicians are using benzodiazepines. GPs perceived that some young adults requested benzodiazepines and suggested this might be because they wanted quick symptom relief. GPs noted that refusing to prescribe felt uncomfortable and that the number of young adults presenting to general practice, already dependent on benzodiazepines, had increased.ConclusionPatient-driven factors for prescribing benzodiazepines suggest there are current unmet treatment needs among young adults with anxiety. Given increases in prescribing in this age group, it may be timely to revisit the role of benzodiazepines in the management of people with anxiety in primary care.

Scottish investment giant abrdn has sold its Focus Solutions software business and is said to be eyeing other potential disposals

This week we learn not to disturb Kelley's special demon slaying time, get too attached to dogs in games, or disturb the Harvest Moon plushie announcement. We also get your suggestions for series that need to be resurrected. Enjoy Action RPG August!

The post RPG Cast – Episode 552: “Aw ***t, She’s Playing Diablo!” appeared first on RPGamer.

Kelley ruins Warcraft by including Conker. Chris mortgages his Xbox. Josh's cat won't let him control his Xbox. And Microsoft has announced their new Candy Crush themed Windows 12.

The post RPG Cast – Episode 615: “The New Dialga Looks Like My Brother’s Broken Vacuum Cleaner” appeared first on RPGamer.

Kelley graduates from Canada. Josh discovers Tactics Advance is an isekai. Meanwhile Chris calculates the skill check for suplexing a train.

The post RPG Cast – Episode 619: “That One Time I Got Reincarnated as a Canadian Yankee in King Arthur’s Court” appeared first on RPGamer.

Josh uses a cat carrier as an impromptu shield. Kelley learns that her husband's Steamdeck RNG is improved if she's not around. Meanwhile, Chris's turtles are always having mating season.

The post RPG Cast – Episode 631: “God of Diablo” appeared first on RPGamer.

Kelley is a complicated person when it comes to PC gaming. Josh is a quiet English man, slightly constipated. And Chris takes a Steam Deck to the face.

The post RPG Cast – Episode 649: “Away With You, Stadia!” appeared first on RPGamer.

It's Extra Life Weekend baby! Phil puts Chris in a closet while Anna states that it's not because she's Canadian, it's because she's a cheap bitch. Meanwhile, the treasure chest looks back at Kelley with an expression that says "...Bruh."

The post RPGCast – Episode 654: “You Canadian” appeared first on RPGamer.

Chris is hunting bears, because of course that's what you do. Kelley hangs out with Chadley and the massively annoying individual. Robert is all about that exquisite fraisier cake.

The post RPG Cast – Episode 716: “Canadian Telephone Game” appeared first on RPGamer.

Chris requires pirate games to be on the ocean. Kelley's over capybaras. Josh is betrayed by his potato peeler's safety guard. Also, everybody hates Wakka.

The post RPG Cast – Episode 737: “India’s Best Divorce Lawyer” appeared first on RPGamer.

EA Sports FC 25 has debuted in first place on the Canadian charts for September 2024, according to data from Circana (formerly The NPD Group) reported by the Entertainment Software Association of Canada (ESA).

There were four other new releases in the top 10 with NHL 25 debuting in second place, The Legend of Zelda: Echoes of Wisdom in third place, Astro Bot in fourth place, and NBA 2K25 in 10th place.

Star Wars: Outlaws is in fifth place, Hogwarts Legacy is in sixth place, and Madden NFL 25 is in seventh place. God of War: Ragnarök is in eighth place following the release of the PC version and Elden Ring is in ninth place.

Top 10 best-selling games in Canada:

1. EA Sports FC 25 - NEW
2. NHL 25 - NEW
3. The Legend of Zelda: Echoes of Wisdom* - NEW
4. Astro Bot - NEW
5. Star Wars: Outlaws
6. Hogwarts Legacy
7. Madden NFL 25
8. God of War: Ragnarök
9. Elden Ring
10. NBA 2K25* - NEW

*Digital sales not included

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463027/ea-sports-fc-25-debuts-in-1st-on-the-canadian-charts/

ublisher Bethesda Softworks and developer MachineGames have released a gameplay deep dive video for Indiana Jones and the Great Circle that is nearly 15 minutes in length.

"From locations and puzzles to gear and combat, MachineGames Audio Director, Pete Ward, takes us on a whirlwind journey through the world of The Great Circle," reads the description to the video. "Get ready for launch with this look at Indy’s grand adventure."

View the gameplay deep dive below:

Indiana Jones and the Great Circle will launch for the Xbox Series X|S, PC via Steam and Microsoft Store, and Xbox Game Pass on December 9.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463033/indiana-jones-and-the-great-circle-gets-gameplay-deep-dive/

While we're getting a Gears Of War prequel in Gears Of War: E-Day, this does mean that Gears Of War 6 is yet to be a thing. In a recent episode of IGN's Podcast Unlocked, former Gears Of War director and current Diablo 4 lead Rod Fergusson revealed what his plans were for Gears 6 when he left. In short, he was going to take the game to space. Righto.

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Putting aside my natural annoyance at Metal Gear Solid Delta: Snake Eater for almost beating out the Twarhammer series in the headline real estate wars, I am more than a little excited to play. Some days, you simply must feast on a tree frog, and while we still don’t have a solid release date, that day doesn’t feel too far away. Good news for stealth fans, and perhaps gooder news for a dozen strapline writers sweating profusely, soiling themselves in anticipation of using “kept you waiting, huh?”.

Until then, I at least have a steady drip feed of new information to keep me sated, the latest of which is the substantial hint that there'll be some new dialogue in the game, as per the video below. Alongside that, the previously pseudonymous Suzetta Miñet - who was credited with voicing EVA in MGS3 and Peace Walker - has revealed herself to be Jodi Benson, the voice of Ariel in Disney’s The Little Mermaid. Cheers for the spot, Automaton West.

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GeForce Now, Nvidia’s PC-focused game streaming service, will begin calling time on its most muscular of power users. A post on the GFN subreddit announced the introduction of a 100-hour monthly cap (or "allowance"), effective from January 1st 2025 for anyone who signs up after that date. Existing streamists, or anyone who signs up by the end of 2024, will get a year’s grace period before the limit kicks in from January 2026.

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After nearly a year of public beta honing, the Nvidia App – Team Green’s new one-stop shop for desktop GPU management – is out in full. Not alongside the upcoming RTX 50 series, as rumoured, but right-now-today-this-minute. I’ve been testing out the launch version and while it’s not without some dud features, it does agreeably achieve its stated goal of combining the functions within Nvidia Control Panel and GeForce Experience. And if installing it means never having to use the latter again, well, that’s 149MB well spent.

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Between 2005 and 2021, Facebook, Twitter and YouTube were more likely to make policy changes in the weeks after negative stories in the media

Just under 5 per cent of the Wikipedia pages in English that have been published since ChatGPT's release seem to include AI-written content

A pediatrician, author and co-inventor of a low-cost COVID-19 vaccine warns that the anti-vaccine movement has morphed into a political force that threatens the world's gains against deadly childhood infections like measles.

Voice assistants may cause confusion across devices. Tech expert Kurt “CyberGuy" Knutsson offers some solutions to fix it.

… Junior Asia/ Oceania Davis Cup and Fed Cup final qualifying event. The … players selected for the Junior Davis Cup include Dev V. Javia, Sandeep … Gogoi (reserve). The Junior Fed Cup team includes Anisha Kashyap, Bhakti … Junior Asia/ Oceania Junior Davis Cup will begin in Kuching, Malaysia ….

The company behind Pornhub and other popular pornographic sites broke Canadian privacy law by allowing intimate images to be shared on its websites without the direct knowledge or consent of everyone depicted, the federal privacy commissioner has ruled. The Office of the Privacy Commissioner’s (OPC) investigation into Aylo (formerly MindGeek), one of the world’s largest […]

How private is your internet address? Very, says the Supreme Court of Canada. Police can’t just walk into a company and demand a suspect’s IP address by saying a Canadian resident doesn’t have an expectation of privacy of that information, the court ruled today. An IP address is vital enough that every resident expects it […]

In Canada, your IP address has the right to remain silent. Elon Musk is suing OpenAI for not being Open. Apple faces a class action not allowing competitive access to backup services and the World Server Throwing Competition in March 2024 is accused of being too violent towards servers.   All this and more on the […]

Artificial intelligence can be the key to unlocking better relationships with work, HP revealed in its new Work Relationship Index (WRI) report. “AI represents a significant opportunity to transform our work dynamics and unlock a more positive and productive environment for all,” stated Dave Shull, president of HP Workforce Solutions at HP Inc.. “To foster […]

Red and processed meat, and even poultry, seem to raise the risk of developing type 2 diabetes, according to a study of nearly 2 million adults, but not everyone is convinced

A new test spots Lyme disease faster than the existing go-to approach and, if approved, could reduce the risk of complications

Narratives around addiction often reduce it to a series of poor choices, lack of values and weakness. This has real-world consequences, warns Anna Wolfe

Levels of certain cells, fatty molecules and proteins in the blood are different in people with chronic fatigue syndrome than in those without it, which could help doctors spot the condition sooner

ALS, the most common form of motor neuron disease, can take a long time to diagnose, but a blood test could help doctors spot the condition sooner

A chemical produced by gut bacteria could be the basis for a non-invasive test for endometriosis – and mouse experiments suggest it might also help treat the condition

People who went from using social media for at least 2 hours a day to just 30 minutes a day reported no improvement to their sleep or emotional well-being

Cases of prostate cancer are surging alarmingly around the world. Thankfully, we are developing more accurate tests that can catch the condition early

Social media commentators claimed Jill Biden refused to look at Vice President Harris as they were seated together at Arlington Cemetery for a Veterans' Day Remembrance.

Listings outpace demand in Toronto and Vancouver

Stock and bond markets are already reacting in anticipation of the changes

Dallas Mavericks minority owner Mark Cuban returned to the Bluesky social media platform with a post after weeks of contentious X posts.

The Canadian women's soccer team was implicated in a drone scandal this past summer. But, an investigation determined drone use against opponents, predated the Paris Olympics.